The goal of this study is to investigate effects of memantine on neuronal structure and fear conditioning in Tg2576 mice. Memantine is an uncompetitive NMDA receptor antagonist and is widely prescribed for the treatment of moderate to severe Alzheimer's disease. Memantine has been hypothesized to have neuroprotective properties, but there are also concerns that it may also be neurotoxic like other NMDA receptor antagonists. Therefore, this study assessed both neuroprotective and neurotoxic potential using quantitative light and electron microscopy on longterm (6 months) administration of different doses of memantine (5, 10, and 20 mg/kg) on plaque deposition, neuronal morphology, and fear conditioning. In this study, the two higher doses (10 and 20 mg/kg) of memantine were associated with decreased amyloid plaque deposition, increased synaptic density, and degenerating axons - the latter two effects independent of genotype. Low dose (5 mg/kg) memantine was associated with decreased plaque deposition, increased synaptic density, and no increase in degenerating axons. However, no dose of memantine improved behavioral deficits. This study suggests that chronic memantine treatment may have both neuroprotective and neurotoxic effects.